Although nucleosides and nucleotides have a good safety record for the treatment of hepatitis B, there have been no systematic reviews on this topic. We searched Medline to include studies of the oral antiviral agents for hepatitis B and adverse events, with at least 48 weeks of follow-up from the initiation of treatment with the drug. Important toxicities include nephrotoxicity, myopathy, and resistance. It is often difficult to ascertain whether an adverse effect is from the study drug or the natural progression of the disease. Further safety data are needed for the newer agents and for all agents with regard to patients with decompensated liver disease, renal dysfunction, the elderly, children, and pregnant women.

BACKGROUND AND AIMS: The extent of healthcare barriers and its association with acute care use among adults with chronic liver disease (CLD) relative to other chronic conditions remains understudied. We compared the probability of barriers and recurrent acute care use among persons with CLD and persons with chronic obstructive pulmonary disease (COPD) and/or cardiovascular disease (CVD). METHODS: We assembled a population-based, cross-sectional study using pooled self-reported National Health Interview Survey data (2011-2017) among community-dwelling persons. Probability of barriers by disease group (CLD vs COPD/CVD) was assessed using hurdle negative binomial regression. RESULTS: The sample included 47,037 adults (5062 with CLD, 41,975 with COPD/CVD). The CLD group was younger (median age 55 vs 62 years) and included more Hispanics (17.5% vs 8.6%) and persons with poverty (20.1% vs 15.3%) than the COPD/CVD group. More respondents with CLD vs COPD/CVD reported barriers (44.7% vs 34.4%), including unaffordability (27.5% vs 18.8%), transportation-related (6.1% vs 4.1%), and organizational barriers at entry to (17.6% vs 13.0%) and within healthcare (19.5% vs 14.2%). While adults with CLD were more likely to experience at least 1 barrier (adjusted incident rate ratio, 1.12 [1.01-1.24], P = .03), they were not associated with more (1.05 [1.00-2.71], P = .06). Probability of recurrent acute care use was associated with more healthcare barriers. CONCLUSION: Findings from this nationally representative sample of over 43 million US adults reveal that persons with CLD have increased probability of healthcare barriers, likely related to their higher prevalence of socioeconomic vulnerabilities compared to persons with COPD/CVD. CLD warrants attention as a priority condition in public policies that direct resources towards high-risk populations.

Aim

To determine whether successful treatment with directacting antivirals (DAA) is associated with improvements in hemoglobin A1c (HbA1c) and if type 2 diabetes mellitus (T2DM) or metabolic syndrome affects sustained virologic response (SVR).

Methods

We performed a retrospective analysis of all hepatitis C virus (HCV) patients at the VA Greater Los Angeles Healthcare System treated with varying DAA therapy between 2014-2016. Separate multivariable logistic regression was performed to determine predictors of HbA1c decrease ≥ 0.5 after DAA treatment and predictors of SVR 12-wk post treatment (SVR12).

Results

A total of 1068 patients were treated with DAA therapy between 2014-2016. The presence of T2DM or metabolic syndrome did not adversely affect SVR12. 106 patients had both HCV and T2DM. Within that cohort, patients who achieved SVR12 had lower mean HbA1c pre treatment (7.35 vs 8.60, P = 0.02), and lower mean HbA1c post-treatment compared to non-responders (6.55 vs 8.61, P = 0.01). The mean reduction in HbA1c after treatment was greater for those who achieved SVR12 than for non-responders (0.79 vs 0.01, P = 0.03). In adjusted models, patients that achieved SVR12 were more likely to have a HbA1c decrease of ≥ 0.5 than those that did not achieve SVR12 (adjusted OR = 7.24, 95%CI: 1.22-42.94).

Conclusion

In HCV patients with T2DM, successful treatment with DAA was associated with a significant reduction in HbA1c suggesting that DAA may have a role in improving insulin sensitivity. Furthermore, the presence of T2DM or metabolic syndrome does not adversely affect SVR12 rates in patients treated with DAA.

Aim

To evaluate and validate the national trends and predictors of in-patient mortality of transjugular intrahepatic portosystemic shunt (TIPS) in 15 years.

Methods

Using the National Inpatient Sample which is a part of Health Cost and Utilization Project, we identified a discharge-weighted national estimate of 83884 TIPS procedures performed in the United States from 1998 to 2012 using international classification of diseases-9 procedural code 39.1. The demographic, hospital and co-morbility data were analyzed using a multivariant analysis. Using multi-nominal logistic regression analysis, we determined predictive factors related to increases in-hospital mortality. Comorbidity measures are in accordance to the Comorbidity Software designed by the Agency for Healthcare Research and Quality.

Results

Overall, 12.3% of patients died during hospitalization with downward trend in-hospital mortality with the mean length of stay of 10.8 ± 13.1 d. Notable, African American patients (OR = 1.809 vs Caucasian patients, P < 0.001), transferred patients (OR = 1.347 vs non-transferred, P < 0.001), emergency admissions (OR = 3.032 vs elective cases, P < 0.001), patients in the Northeast region (OR = 1.449 vs West, P < 0.001) had significantly higher odds of in-hospital mortality. Number of diagnoses and number of procedures showed positive correlations with in-hospital death (OR = 1.249 per one increase in number of procedures). Patients diagnosed with acute respiratory failure (OR = 8.246), acute kidney failure (OR = 4.359), hepatic encephalopathy (OR = 2.217) and esophageal variceal bleeding (OR = 2.187) were at considerably higher odds of in-hospital death compared with ascites (OR = 0.136, P < 0.001). Comorbidity measures with the highest odds of in-hospital death were fluid and electrolyte disorders (OR = 2.823), coagulopathy (OR = 2.016), and lymphoma (OR = 1.842).

Conclusion

The overall mortality of the TIPS procedure is steadily decreasing, though the length of stay has remained relatively constant. Specific patient ethnicity, location, transfer status, primary diagnosis and comorbidities correlate with increased odds of TIPS in-hospital death.

Currently, no disease-targeted instrument is available for measuring health-related quality of life (HRQOL) in liver transplant recipients. We developed and tested a post-liver transplant quality of life (pLTQ) instrument. Item selection for the pLTQ instrument was based on responses from liver transplant recipients, 12 liver experts, and a literature search. Impact scores were generated, and a factor analysis was conducted to organize the items into domains. Questions were constructed for each item, and redundant questions were removed. The pLTQ instrument was initially administered to 196 liver transplant patients and then was again administered to 77 patients 6 to 9 months later with a generic HRQOL survey [Medical Outcomes Study Short Form 36 (SF-36)]. Analysis of variance was used to compare the scores of patients at different times since transplantation and with various indications for transplantation. After redundancies were eliminated, the pLTQ instrument included 32 items in 8 domains: Emotional Function, Worry, Medications, Physical Function, Healthcare, Graft Rejection Concern, Financial, and Pain. We found stable pLTQ instrument and SF-36 instrument scores over time. Data 6 to 9 months after the initial assessment indicated stable quality of life outcomes. The pLTQ instrument is applicable to a variety of liver transplant recipients. The questionnaire was tested with a cross-sectional and longitudinal approach.

Background

Fibrosing cholestatic hepatitis (FCH) is an uncommon but potentially fatal complication of recurrent hepatitis C (HCV) in liver transplant recipients.

Methods

We matched the treatment outcomes of 10 liver transplant recipients who developed FCH with those of 10 recipients with recurrent HCV without FCH treated with sofosbuvir and ribavirin.

Results

Baseline mean alanine transaminase, aspartate transaminase, alkaline phosphatase, and total bilirubin were 186 U/L, 197 U/L, 243 U/L, and 6.7 mg/dL, respectively, in the FCH recipients and 82 U/L, 60 U/L, 110 U/L, and 0.99 mg/dL, respectively, in non-FCH recipients. The sustained viral response in FCH and non-FCH recipients was 40% and 80%, respectively. One-yr patient and graft survival rates were 90% and 80%, respectively, in FCH recipients, and 100% in non-FCH recipients. Seven FCH and six non-FCH recipients were treated for anemia with blood transfusion and/or erythropoietin growth factors.

Conclusion

Our results suggest that the use of sofosbuvir and ribavirin is effective and tolerable in liver transplant recipients treated for recurrent FCH. There is a trend of lower sustained viral response, patient survival, and graft survival in the FCH recipients.

Hepatic encephalopathy (HE) is normally diagnosed by neuropsychological (NP) tests, which are not very specific and do not reveal the underlying pathology. Magnetic resonance imaging (MRI) and spectroscopy (MRS) of the brain offer alternative and possibly more specific markers for HE. These methods were applied in conjunction with NP testing in order to determine their usefulness in the identification of HE and to understand the pathogenesis of HE more clearly. MR imaging and spectroscopy examinations, in addition to a battery of 15 NP tests, were administered to investigate 31 patients awaiting liver transplantation and 23 healthy controls. MR image intensities from the globus pallidus region were calculated and normalized to those of the thalamus. Absolute concentrations and ratios with respect to creatine (Cr) of several metabolites were computed from MR spectra. The MR data were correlated with the results of NP tests. The patients showed impairment in NP tests of attention and visuospatial and verbal fluency. In T1-weighted MRI, the relative intensity of the globus pallidus with respect to that of the thalamus region was significantly elevated in patients and correlated(negatively) with three NP tests (Hooper, FAS, and Trails B). The absolute concentrations of myo-inositol (mI) and choline (Ch) were significantly reduced in three brain regions. In addition, the absolute concentrations of glutamine (Gln) and combined glutamate and glutamine (Glx) were increased in all three locations, with Gln increase being significant in all areas while that of Glx only in the occipital white matter. In summary, this study partially confirms a hypothesized mechanism of HE pathogenesis, an increased synthesis of glutamine by brain glutamate in astrocytes due to excessive blood ammonia, followed by a compensatory loss of myo-inositol to maintain astrocyte volume homeostasis. It also indicates that the hyperintensity observed in globus pallidus could be used as complementary to the NP test scores in evaluating the mental health of HE patients.

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease. HCV cure has been linked to improved patient outcomes. In the era of direct-acting antivirals (DAAs), HCV cure has become the goal, as defined by sustained virological response 12 weeks (SVR12) after completion of therapy. Historically, African-Americans have had lower SVR12 rates compared to White people in the interferon era, which had been attributed to the high prevalence of non-CC interleukin 28B (IL28B) type. Less is known about the association between race/ethnicity and SVR12 in DAA-treated era. The aim of the study is to evaluate the predictors of SVR12 in a diverse, single-center Veterans Affairs population. We conducted a retrospective study of patients undergoing HCV therapy with DAAs from 2014 to 2016 at the VA Greater Los Angeles Healthcare System. We performed a multivariable logistic regression analysis to determine predictors of SVR12, adjusting for age, HCV genotype, DAA regimen and duration, human immunodeficiency virus (HIV) status, fibrosis, nonalcoholic fatty liver disease (NAFLD) fibrosis score, homelessness, mental health, and adherence. Our cohort included 1068 patients, out of which 401 (37.5%) were White people and 400 (37.5%) were African-American. Genotype 1 was the most common genotype (83.9%, N = 896). In the adjusted models, race/ethnicity and the presence of fibrosis were statistically significant predictors of non-SVR. African-Americans had 57% lower odds for reaching SVR12 (adj.OR = 0.43, 95% CI = 1.5-4.1) compared to White people. Advanced fibrosis (adj.OR = 0.40, 95% CI = 0.26-0.68) was also a significant predictor of non-SVR. In a single-center VA population on DAAs, African-Americans were less likely than White people to reach SVR12 when adjusting for covariates.

Background

Hepatocellular carcinoma (HCC) is a common primary liver cancer with poor overall survival. We hypothesized that there are HCC-associated cell-types that impact patient survival.

Methods

We combined liver single nucleus (snRNA-seq), single cell (scRNA-seq), and bulk RNA-sequencing (RNA-seq) data to search for cell-type differences in HCC. To first identify cell-types in HCC, adjacent non-tumor tissue, and normal liver, we integrated single-cell level data from a healthy liver cohort (n = 9 non-HCC samples) collected in the Strasbourg University Hospital; an HCC cohort (n = 1 non-HCC, n = 14 HCC-tumor, and n = 14 adjacent non-tumor samples) collected in the Singapore General Hospital and National University; and another HCC cohort (n = 3 HCC-tumor and n = 3 adjacent non-tumor samples) collected in the Dumont-UCLA Liver Cancer Center. We then leveraged these single cell level data to decompose the cell-types in liver bulk RNA-seq data from HCC patients' tumor (n = 361) and adjacent non-tumor tissue (n = 49) from the Cancer Genome Atlas (TCGA) multi-center cohort. For replication, we decomposed 221 HCC and 209 adjacent non-tumor liver microarray samples from the Liver Cancer Institute (LCI) cohort collected by the Liver Cancer Institute and Zhongshan Hospital of Fudan University.

Results

We discovered a tumor-associated proliferative cell-type, Prol (80.4% tumor cells), enriched for cell cycle and mitosis genes. In the liver bulk tissue from the TCGA cohort, the proportion of the Prol cell-type is significantly increased in HCC and associates with a worse overall survival. Independently from our decomposition analysis, we reciprocally show that Prol nuclei/cells significantly over-express both tumor-elevated and survival-decreasing genes obtained from the bulk tissue. Our replication analysis in the LCI cohort confirmed that an increased estimated proportion of the Prol cell-type in HCC is a significant marker for a shorter overall survival. Finally, we show that somatic mutations in the tumor suppressor genes TP53 and RB1 are linked to an increase of the Prol cell-type in HCC.

Conclusions

By integrating liver single cell, single nucleus, and bulk expression data from multiple cohorts we identified a proliferating cell-type (Prol) enriched in HCC tumors, associated with a decreased overall survival, and linked to TP53 and RB1 somatic mutations.

Background and aims

All-oral interferon-free antivirals are highly effective in treating recurrent hepatitis C (HCV) infection in liver transplant (LT) recipients. The aim of the study was to assess immunosuppression needs after achieving a sustained viral response (SVR).

Methods

We compared immunosuppression needs before and after achieving a SVR in adult LT recipients treated for recurrent HCV infection with all-oral direct acting agents.

Results

We identified 52 liver LT treated recipients who achieved a SVR. The median (25th and 75th percentile interquartile range [IQR]) age was 62 years (57.75, 65). Most recipients received tacrolimus (TAC) for their immunosuppressant regimen. After achieving SVR, there was no statistically significant difference in daily dose of TAC unadjusted per weight (p > 0.05). However, there was a statistically significant decrease in daily dose of TAC adjusted per weight, serum levels of TAC, and the product of glomerular filtration rate and TAC. No statistically significant differences in cyclosporine unadjusted/adjusted per weight daily dose or serum levels were noted.

Conclusions

Immunosuppression needs were increased for those patients treated with TAC but not cyclosporine. LT recipients prescribed TAC require close monitoring after treatment completion to avoid potential risk of acute rejection.